Age-specific incidences of melanoma in the study populations were similar to national rates. For example, for white women 50–54 years of age, rates were 25 out of 100
in NHS and 27 out of 100
in recent US data (Ries et al, 2002
shows the characteristics of the study populations within low and high categories of vitamin C, vitamin E, retinol, and β-carotene intakes from foods plus supplements. For all nutrients, NHS women with higher intakes were older, and if postmenopausal, were more likely to use postmenopausal hormones. NHS II women with higher intakes were more likely to be nulliparous. In both cohorts, the nondietary risk factors for melanoma were not associated with nutrient intakes. Use of multivitamins and vitamin C and E supplements were high in both cohorts (53, 35, 36%, respectively, for NHS in 1998; 51, 27, 21%, respectively, for NHS II in 1999). Vitamin A (<5%) and β-carotene (<3%) supplement use were low in both cohorts.
We found no evidence that higher intakes of vitamin C, vitamin E, retinol, or β-carotene, the major carotenoid with provitamin A activity, are associated with a lower risk of melanoma (
). Specific tocopherols (α-tocopherol, β-tocopherol, δ-tocopherol, γ-tocopherol) and other carotenoids, with or without provitamin A activity (α-carotene, lycopene, β-cryptoxanthin, lutein, and zeaxanthin), were also unrelated to risk (data not shown). Age-adjusted relative risks were only modestly attenuated when adjusted for the other melanoma risk factors.
Relative risks (RRs) of melanoma by daily intakes of vitamin C, vitamin E, retinol, and β-carotenea
Rather than the hypothesised inverse relation, we observed a positive association between dietary vitamin C and melanoma. Women with intakes
had an RR of 1.43 (95% CI 1.02–2.00) compared to those with intakes <90
. The dose – response association was also marginally significant (P
=0.05). A significant linear relation remained when vitamin E, retinol, and β
-carotene were added to the model (P
We also examined nutrient supplements in relation to melanoma risk (
). Current use of multivitamins (a major source of retinol), and supplements of vitamins C and E were all unassociated with risk, and there was also no indication of benefit with longer duration of use. Vitamin A and β-carotene supplement use were too low to provide sufficient power for analysis.
Relative risks (RRs) of melanoma by use of vitamin supplementsa
Total fruits and vegetables or those with a high carotenoid content (
) were also not associated with a lower risk of melanoma (
) (see Feskanich et al (2000)
for a description of the fruits and vegetables). However, consumption of fruits and vegetables high in vitamin C (
) was significantly associated with an increasing risk (P
for linear trend=0.01). Orange juice was the major contributor to dietary vitamin C (about 20% in both cohorts), and
was associated with an elevated risk of melanoma when compared to no orange juice consumption (RR=1.61, 95% CI 0.92–2.84, P
for linear trend=0.008). In the NHS cohort, women recalled their frequency of orange juice consumption during high school, and this too was associated with an increased risk of melanoma (RR= 1.59, 95% CI 1.17–2.18 for
). When analysed in the same model, significant positive dose–response relations were observed for both adult (P
=0.01) and high school (P
=0.04) orange juice consumption. In an analysis of consistent intake over time, women who reported that they consumed
of orange juice in both high school and as an adult had an RR of 2.32 (95% CI 1.36–4.00) compared to those who reported <1 serving week−1
in both time periods.
Relative risks (RRs) of melanoma by daily servings of fruits and vegetables and by frequency of consumption of orange juicea
Since dietary vitamin C was not expected to be a risk factor for melanoma, we speculated that the positive associations might be because of greater sun exposure among women with higher vitamin C intakes. The highest incidences of melanoma were found among the NHS women who lived in Florida (43 out of 100
) and California (31 out of 100
), states where excessive sun exposure is more likely. However, their dietary intakes of vitamin C were not higher than the rest of the cohort and excluding them from analyses did not change results from those in that were adjusted for state of residence.
Since nondietary determinants of melanoma contribute significantly to risk, we examined associations between vitamins A, C, E, and melanoma separately among women at higher and lower risk based upon nondietary factors. A total risk score was calculated using cohort-derived RRs associated with each of the five nondietary factors listed in . The lowest score of 5 was assigned to women with the lowest relative risk (RR=1.0) for all factors; the highest risk scores were 11.9 in NHS and 14.3 in NHS II. Categories of low, middle, and high risk were defined to ensure approximately equal numbers of cases in each category.
shows results for dietary vitamin C and total retinol, the only nutrients which exhibited possible interactions with the risk score. For dietary vitamin C, a significant positive association was found only among women in the high-risk category (P
for linear trend=0.01), although the test for interaction was not significant (P
=0.12). For total retinol, a significant inverse association was observed in the low-nondietary-risk category. An RR of 0.39 (95% CI 0.22–0.71) was associated with a total retinol intake of
when compared to <400μ
for linear trend=0.01) and there was a significant interaction between total retinol and risk score (P
Relative risks (RR) of melanoma by daily intakes of dietary vitamin C and total retinol, stratified by risk based on nondietary factorsa